Foxo1-induced miR-92b down-regulation promotes blood-brain barrier damage after ischaemic stroke by targeting NOX4

The blood-brain barrier (BBB) damage is a momentous pathological process of ischaemic stroke. NADPH oxidases 4 (NOX4) boosts BBB damage after ischaemic stroke and its expression can be influenced by microRNAs. This study aimed to probe into whether miR-92b influenced the BBB damage after ischaemic stroke by regulating NOX4 expression. Here, miR-92b expression was lessened in the ischaemic brains of rats and oxygen-glucose deprivation (OGD)-induced brain microvascular endothelial cells (BMECs). In middle cerebral artery occlusion (MCAo) rats, miR-92b overexpression relieved the ameliorated neurological function and protected the BBB integrity. In vitro model, miR-92b overexpression raised the viability and lessened the permeability of OGD-induced BMECs. miR-92b targeted NOX4 and regulated the viability and permeability of OGD-induced BMECs by negatively modulating NOX4 expression. The transcription factor Foxo1 bound to the miR-92b promoter and restrained its expression. Foxo1 expression was induced by OGD-induction and its knockdown abolished the effects of OGD on miR-92b and NOX4 expressions, cell viability and permeability of BMECs. In general, our findings expounded that Foxo1-induced lessening miR-92b boosted BBB damage after ischaemic stroke by raising NOX4 expression.

Automated summary

The study showed that miR-92b influences the BBB damage after ischaemic stroke by regulating NOX4 expression, while Foxo1 is involved in this process by controlling the expression of miR-92b.